Roozbeh Yalfani,1,*
1. Department of Nursing, Faculty of Medical Sciences, Islamic Azad University,Varamin-Pishva branch, Tehran, Iran
Introduction: Talaromycosis (formerly known as Penicilliosis) is an infection caused by Talaromyces marneffei, a thermally dimorphic fungus formerly known as Penicillium marneffei. In 1956, the first case of T. marneffei infection in bamboo rats was studied, and subsequently in 1973, the first case in humans was reported. Among the hundreds of Talaromyces species, Talaromyces (Penicillium) marneffei is
the only thermally dimorphic species known to be pathogenic to mammals, including humans. T. marneffei is a primary lung pathogen that disseminates to other internal organs
by lymphatic or hematogenous mechanisms. It causes disseminated disease in both immunocompetent and immunocompromised individuals, though it is most prevalent in patients with HIV/AIDS as well as patients with functional impairments of cellular immunity, particularly defects in CD4 T cell activity. T. marneffei grows as a saprophytic mold in the environment, but undergoes phase transition to a pathogenic yeast-like cell at mammalian physiologic temperatures.
Methods: Talaromycosis is an important invasive mycosis caused by Talaromyces marneffei. The World Health Organization and Food and Drug Administration have recently paid increasing attention to the disease as a neglected tropical disease due to the growing burden of T. marneffei infection globally. Talaromycosis is a common opportunistic disease and a leading cause of death in patients with acquired immune deficiency syndrome (AIDS) in endemic regions; moreover, it is increasingly being reported in human immunodeficiency virus (HIV)- negative individuals and outside of epidemic areas. The mortality of talaromycosis is up to 30% in both HIVpositive and HIV-negative individuals, which is associated with late diagnosis and untimely or ineffective antifungal therapy. Therefore, early diagnosis and effective antifungal treatment are critical to reduce the mortality.
Results: Talaromycosis is an invasive fungal infection which can be localized to the upper or lower respiratory tract, bones, joints, and intestinal tract, or disseminated across multiple organ systems. The main clinical manifestation of talaromycosis is skin lesions which are characterized by raised bumps (usually small and painless) on the skin, particularly on the face, the neck, and the extremities. Notably, HIV-negative individuals with talaromycosis are less likely to have skin lesions. In the particular context of advanced HIV infection (patients with CD4+ T-cells < 200 cells/μL), talaromycosis disseminates to organs such as the lung, liver, spleen, gastrointestinal tract, blood stream, and bone marrow. Interestingly, some reports have indicated that T. marneffei may cause primary pulmonary talaromycosis even in apparently healthy individuals, which suggests that talaromycosis may well be a more common cause of pneumonia in endemic areas than has been hitherto assumed.
Conclusion: The mechanisms for the pathogenesis of talaromycosis are not definitively established.
However, fungal morphogenesis appears to be a crucial virulence factor in the establishment of infection. Evidence suggests that aerosolized infectious particles (conidia) from environmental disturbances, especially in tropical monsoon seasons, are acquired via inhalation. After inhalation, the sizes of conidia (2 to 3 _m in diameter) allow them to infiltrate deeply into the lung alveoli. Once in the lung, these infectious propagules undergo phase transition into the parasitic yeast form, which are rapidly ingested by lung phagocytes. In healthy individuals, engulfed conidia are, for example, killed by host macrophages through the production of oxidative burst as well as the action of lysosomal enzymes. However, as with other pathogenic fungi such as Histoplasma, T. marneffei can survive and replicate inside the phagosomal compartment of macrophages. Hence, T. marneffei is classified as a facultative intracellular pathogen as it is found inside macrophages and tissue histiocytes in talaromycosis patients. The ability to transition from an environmental mold to a yeast form and resist to killing by host phagocyte is recognized as an important virulence mechanism of dimorphic pathogenic fungi as the switch is challenging to host innate and acquired immune defenses. In particular, the pre-existing impairment of cell-mediated immune responses that occur, for example, in patients with AIDS results in severely reduced fungicidal activity that diminishes the capacity of host phagocytes to eradicate this pathogen.